Study Finds Few Therapies Work Well on Hot Flashes

By DENISE GRADY

Published: May 3, 2006

CORRECTION APPENDED

For women who want a drug to ease menopausal hot flashes but do not want to take hormones, certain antidepressants and other medicines may help, researchers are reporting. But those medicines have side effects, little is known about whether it is safe to take them for a long time and they do not work as well as hormones.

Given the drawbacks, the nonhormonal drugs ''are not optimal choices for most women,'' according to an article being published today in The Journal of the American Medical Association.

That conclusion would seem to leave no optimal choice for most women, a vexing predicament for those who have been searching for a safe alternative to estrogen, and who are tired of being told to sip ice water, dress in layers and turn up the air conditioning.

Researchers estimate that 50 percent of women have hot flashes during menopause and that 20 percent of those affected seek treatment. The flashes -- a sudden sensation of being overheated, with sweating and facial flushing -- can occur repeatedly, day and night. They can disrupt sleep and persist for years, sometimes even decades.

Hormones, once popular, fell from grace in 2002 when a large government study found they increased the risk of blood clots, strokes, heart attacks and breast cancer. Before that, doctors had freely recommended hormones, knowing they would ease menopause symptoms and believing they would also help prevent heart disease and other chronic ailments. The 2002 study shattered those beliefs. Sales plummeted as the number of users dropped to 57 million in 2003 from 91 million in 2001.

Dr. Jeffrey Tice, an internist at the University of California, San Francisco, who wrote an editorial accompanying the study, said: ''With hormones, we really were thinking we were preventing a lot of diseases and it was good for the long term. Maybe we were brainwashed by the industry paying people to tell us that in medical school.''

Now, other drugs have come into use for hot flashes, but not much is known about their effectiveness or long-term safety. Until recently, there was little interest in studying them rigorously, because hormones worked so well for most women.

''There's a lot of hype around trying things that we haven't proven effective and, sadly, we haven't proven they're safe,'' said Dr. Heidi D. Nelson, the first author of the journal article and an internist and professor at the Oregon Health and Science University.

The report is based on a review of 43 studies of various nonhormonal drugs being used for hot flashes. Most were originally approved for other purposes. The drugs include the antidepressants Paxil (paroxetine), Effexor (venlafaxine), Prozac (fluoxetine) and Celexa (citalopram), the blood pressure drug Catapres (clonidine), and the seizure drug Neurontin (gabapentin). Some came into use for menopause because women taking them for other reasons told doctors the drugs seemed to diminish their hot flashes.

The researchers also examined studies of nonprescription extracts from soy and red clover, which contain plant estrogens called isoflavones and are marketed as a ''natural'' treatment for hot flashes.

None of the drugs or extracts are approved by the Food and Drug Administration to treat hot flashes -- only hormones are approved for that purpose -- but doctors are free to prescribe medicines for any use they see fit, and many recommend the drugs or plant products for hot flashes, based on study findings and their patients' experiences.

The researchers found that on average, antidepressants and Catapres each appeared to reduce hot flashes by about one per day, and Neurontin by about two per day. For women with a lot of hot flashes, that is not a very impressive performance, Dr. Nelson said, but she added that the drugs may also lessen their severity.

Estrogen, by comparison, gets rid of two to three flashes a day, and also makes them milder, Dr. Nelson said. Though hormones cause small increases in the risks for breast cancer and heart disease, a short course may still be the best choice for women with very severe symptoms, she said, though she added that women who have had breast cancer should definitely not take hormones.

All the nonhormonal drugs have side effects. The antidepressants can cause headache, nausea, dry mouth, dizziness and insomnia or sleepiness. Catapres can cause some of the same symptoms and also constipation. Neurontin causes sleepiness, and soy extracts can produce gastrointestinal troubles.

Among the antidepressants, Paxil seemed to have the strongest evidence of benefit. There were only two studies for Effexor, just one of which suggested it might help.

For the other antidepressants, Prozac and Celexa, and for the plant extracts, there was no statistically significant evidence that they worked for hot flashes.

''But I wouldn't want any drug company to get an edge,'' Dr. Nelson said. ''It's just where we are today. It's not the end of the story.''

She took a cautious view because she and her colleagues found that there was relatively little reliable data on using the drugs for hot flashes. Of 10 studies on antidepressants, for instance, the researchers judged only two of the studies to be good, and the rest fair or poor. The poor rating often meant a study, even though well conducted, was too small or too short to be conclusive.

''If there were only 20 women in the study, how do we say it's appropriate for all the women in the country?'' Dr. Nelson said.

''Now we know what we need,'' she said. ''More bigger studies on more things.''

In the meantime, both Dr. Tice and Dr. Nelson said that for women who find their symptoms intolerable and want treatment, they would favor antidepressants over hormones. But Dr. Tice warned that the drugs should not be used long term.

''I wouldn't encourage the mindset of putting women on these drugs thinking they're going to be on them for life,'' he said, adding that patients should try the drugs for a few months and then try to stop.

''We hate to medicalize a natural process,'' Dr. Nelson said, but she added that severe symptoms should not be dismissed. ''We want to take it seriously, but not everybody needs to be on prescription drugs for it.''

Correction: May 4, 2006, Thursday
An article yesterday about nonhormonal drug treatments for menopausal hot flashes misstated an index of hormone use in the United States. What dropped to 57 million in 2003 from 91 million in 2001 was the number of prescriptions, not the number of users.